Diabetes Canada and the Canadian Liver Foundation are delighted to present a special webinar for individuals living with and impacted by diabetes and liver disease, featuring Dr. Mary Anne Doyle and Dr. Mark Swain. We will define and explore liver disease, its relationship with diabetes, and steps you can personally take to identify and mitigate risk.
welcome everyone uh thank you for tuning
in my name is brooks roach i am a
diabetes education specialist with
diabetes canada and i'd like to begin by
welcoming you our viewers and
acknowledging that the land from which
i'm calling is the traditional and
unseated territory of migma people so
wherever you are joining this webinar
from i would invite you to just take a
moment and reflect on
the traditional and
and
traditional inhabitants of the lands we
now call canada
i'm really excited to to be with you
today and to present this uh really
exciting collaboration that we've been
developing with a wonderful partner the
the canadian liver foundation um and and
the intent of this webinar as you'll
hear is to discuss some of the
fascinating intersections and prevent to
present you with some actions and
strategies uh recognizing the link
between liver disease and diabetes and
with that i'd like to hand it over to my
colleague from the canadian liver
foundation nem take it away
thank you brooks um hello everyone uh
good afternoon and uh good morning and
good day for everyone who are who is
joining us today for this wonderful
opportunity webinar um as brooks did
mention uh my name is nem i am one of
the senior managers of support and
education the canadian river foundation
i would also like to acknowledge that
our national office for the canada
foundation in markham ontario is
situated upon traditional territories of
the anishinabe peoples and of the haduno
sami peoples covered by the upper canada
treaties
we are joined today by two wonderful
experts we have dr mark swain a
professor of medicine of the professor
medicine and head of division of
gastroenterology and hepatology at the
university of calgary as well as dr
marianne doyle endocrinologist and
associate scientist in clinical
epidemiology at the ottawa hospital an
assistant professor of medicine at the
university of ottawa
welcome and thank you both for being
here
so as brooks mentioned we are going to
be diving into a important conversation
evaluating and discussing relationships
between
liver disease and diabetes and our
experts will be answering some key
questions that we've been hearing from
patients uh we'll also be getting
questions from our viewers and some
questions have already been submit
submitted so thank you everyone who
submitted the questions ahead of time
and you can also ask any of your
questions by replying in the comment
feed below
without further ado i will be turning
the mics over to our experts
great thank you for inviting me today
i'm marianne doyle and um and although
i'm an endocrinologist
here in ottawa i have had an interest in
chronic liver disease probably for the
last 10 to 15 years my interest started
initially with infectious liver disease
so hepatitis c and
specifically hepatitis c and the
relationship between
infectious liver disease and the
incidence and prevalence of diabetes and
that got me thinking about how
really in endocrinology and diabetes
management we really don't pay much
attention to the the liver and got me
shifted my focus i think also too as we
started finding treatments for hepatitis
c there was less interest in that area
but
it shifted my interest more to metabolic
liver disease and the association with
with diabetes
and uh and so i'm happy to be here to
talk with dr swain about that today and
um and answer any questions that anyone
may have
and uh hi everyone i'm mark swain i'm in
calgary and uh uh actually like marianne
my my interest uh traditionally was more
in
sort of infectious types of liver
disease and and autoimmune types of
liver disease and in fact
um uh
fatty liver disease was something that
was actually really
not it was kind of ignored actually in
the liver world for a very long time but
it's become quite clear that not only is
it an entity on its own but it's also
uh a driver for other other forms of
liver disease and making and often makes
them uh more aggressive uh but also the
it's become very clear that it's uh
linked to uh to uh uh mainly type two
diabetes uh and uh and so this
this is a natural kind of uh discussion
uh because
type two diabetes and and and fatty
liver disease are are often not talked
about at the same time but but in fact
they should be because
as you'll see as we go through our uh
our discussion today is that they they
intertwine very
robustly and in fact they need to be
discussed
really together
so thanks for joining us
great thank you
dr swain so i'm going to just start with
some
broad facts about diabetes in canada
i think over the last two years we've
really focused on covid but in all of
that there's been another silent um
disease that's been grumbling along
and i think um we need to take
just a minute to kind of think and look
back at some of those numbers so
interesting one in three canadians in
canada so about 11 million canadians are
actually living with diabetes or
pre-diabetes today and that's an
enormous amount of people
and the burden on our sis our health
care system is is phenomenal um and and
we know that there's a lot that we can
do to prevent this
um and that a canadian is diagnosed
every three minutes so in this talk
today during this hour about 30
canadians will be diagnosed with
diabetes and and again um this
being um
that it is a preventable disease um
really there is a lot more that we can
do
um to mitigate that
um about one and a half canadians one
half million sorry not one and a half
canadians one and a half million
canadians um actually have type 2
diabetes and don't know it and that's
because it really is
a silent disease people can have high
blood sugars for years and years and
years and and not not be aware of it
and then there are about six million
canadians that are living with
pre-diabetes half of which will go on to
develop type 2 diabetes but with
appropriate preventative care we can
prevent that we can change that course
and the real concern with it with
diabetes um is that
it's the the complications that come
from it um and come from the high blood
sugar so we know that it causes the
leading cause of blindness it causes 30
percent of strokes that we see 40
percent of heart attacks
50 of kidney failure that requires
dialysis and then 70 of all
non-traumatic leg and foot amputations
so a real health care concern um that we
can do more to uh to change the the
course of the disease
so i'm going to take just a little step
back here and just go back to some
basics about what is diabetes diabetes
is elevated blood glucose levels
and to understand that we really need to
think about what is plasma glucose and
it's basically a a fine balance between
glucose entering the circulation and
then glucose being removed from the
circulation so what we eat versus the
energy we expend
um and the body requires a constant
source of energy so even though we're
sleeping our body is still using glucose
in our blood and we only eat
intermittently so that balance is
regulated very tightly in fact um by
hormones that are secreted from the
pancreas so we have insulin is which we
talk about most often but also glucagon
and
insulin and glucagon work together to
make sure that that blood glucose level
is is well controlled but there's also a
number of other players that we um that
we need to consider when we're talking
about diabetes so can we move on to the
next slide
so some of the key players are the brain
which in fact uses a
significant amount of our blood um
glucose
levels or
amounts um but it's able to use glucose
independent of insulin it's the only
only organ that is
then there's the pancreas which we um
that which is a key player in in
regulating glucose metabolism through
the secretion of both insulin and
glucagon and again that fine balance
then we have our muscles um which are
important in terms of when we were ready
to exercise and be active then our
muscles are able to use that energy also
able to store some of that energy
also able to use some of that
those circulating blood glucose um with
independent of insulin so the more
active you are the more your your body
will be efficient in in using that that
circulating glucose the kidney is a
really important
player in terms of excreting glucose so
the when glucose levels get high the
body the kidney is able to excrete more
more glucose
and then adipose tissue important in
storage when there's high levels of
glucose around our body's able to
convert fat and store it for a time
where we may need that and store it as
adipose tissue and then what we're pro
we're most interested in today is the
liver and that's probably the the player
that's least talked about but probably
the biggest player in glucose metabolism
so not only is the liver key at making
sure that the body has the proper
glucose levels it needs when it comes
time for
activity energy
is needed
but it's also able to store large
amounts of
glucose and so probably one of the
biggest key players but often neglected
and not focused on as much until
recently
i'm also going to just take a step back
and we we often talk about diabetes be
as as if it's all one disease and
and honestly until recently we have
actually treated um
both type 1 and type 2 diabetes as if
they are um one in the same and i'll get
into the reason the rationale for that
but i think it's important to realize
that there are two separate diseases and
although they're they're both um
referred to as diabetes two very
separate diseases so type one diabetes
is actually an autoimmune disease where
you get destruction of the beta cells
and beta cells are the cells in the
pancreas that are important in producing
insulin and when those get destroyed the
body's no longer able to produce insulin
and no longer has the insulin around
circulating that is needed to help the
body and the cells in the body the liver
take up those circulating glucose levels
and as a result the glucose increases in
the blood and and then becomes toxic to
the the circulating cells and organs
um the exact cause is really not well
understood it's probably a genetic
combination of genetic and perhaps
environmental factors that are
contributing um to this and so really
this is an insulin deficiency problem
and the treatment for this is insulin
in contrast type 2 diabetes the body
does make insulin it's not it has the
cells that are making it or not haven't
been destroyed or anything but the body
can't use it properly it also then
starts over time those cells may start
to fail and produce less insulin
and there's also so there's also there's
insulin resistance but also an
insufficient production to overcome that
insulin resistance
when we're talking about causes or risk
factors we know that as people get older
this seems to be more prevalent obesity
definitely contributes to this
we know that a sedentary lifestyle can
contribute to it there's definitely
certain genetics and it's probably
multiple different genes that are acting
simultaneously
um and then ethnicity definitely
contributes to it the interesting thing
about this is that with lifestyle
modification weight loss
um
certain oral medications and insulin we
can change that
and that's our treatment so it's not
solely oh your insulin isn't working we
need to give you more well that which is
what we sometimes do but that isn't our
main
treatment and it isn't our first our
go-to treatment
type one diabetes is really not
preventable at this point because we
don't fully understand the cause and it
really only accounts for about 10 of the
cases in contrast type 2 diabetes is
preventable um in in many cases and it
accounts for about 90 of diabetes cases
mary and pardon the interruption we just
have a few folks who are commenting in
on facebook that they're not able to
actually see the the live feed so if you
don't mind we're just going to pause for
a moment and reconnect to that live
stream sure
there's not a zoom webinar without a
technical issue
okay folks it looks like we are back so
i will uh
hit next slide and then hand the reins
back over to you
all right great
um so i just was talking about the
differences between type 1 and type 2
diabetes and really our focus today is
going to be on type 2 diabetes and not
the association between type 2 diabetes
and
metabolic liver disease because they're
probably
uh and dr swain will go into to this a
little bit more but um
either
in intertwined or related or maybe even
spectrum of the the same disorder and so
that's what our focus is really going to
be on and so when we're looking at and
this is just a little bit of a diagram
to sort of explain
what's happening when we we have type 2
diabetes so
as i mentioned there's insulin
resistance
and as a result you get decreased uptake
of glucose in in the body so a decrease
uptake in the muscle decrease uptake in
adipose tissue you get higher levels of
glucose circulating you also have beta
cell dysfunction
and so the
the beta cells the insulin secreting
cells in the pancreas are not able to
overcome this resistance and as a result
there's less insulin there's still
insulin but there's less insulin
circulating for the level of the
the blood sugars are at and as a result
all of these factors contribute to
higher blood sugar levels
um the
liver is also
not recognizing necessarily that there
is
um
high these high levels because the body
is is in need of glucose and not
entering the cells so it actually also
leads to increased glucose output so
there's basically dysregulation between
the pancreas the liver the muscle and
adipose tissue so all of the key players
in in the body
in glucose metabolism
and what does that what
why does this matter so we know that
with higher blood sugar levels and this
is important in type 1 and type 2
diabetes but when the blood sugar levels
are high over time
these high levels of glucose are
actually toxic to the cells and organs
of our body and as a result this leads
to
a lot of macrovascular complications so
it puts people at higher risk of stroke
heart disease and hypertension
it leads to
peripheral vascular disease so narrowing
of the blood vessels
that supply the feet and toes and
fingers and and arms and as a result
can lead to increased risk of infection
also increased risk of amputation
there's also microvascular complications
so the smaller vessels that supply the
eye um are quite sensitive to high blood
sugar levels and as a result this can
lead to changes in the retina so the
back of the eye as well as increased
risk of cataracts
high circulating glucose levels are also
quite toxic to the kidneys and as a
result this puts people at risk for a
renal disease
and over time slowly the kidneys start
to fail and they're no longer able to um
to function and and
clear the blood like they should
and and patients end up
needing dialysis
it also destroys the small um little
nerves that supply that um we depend on
for
uh sensitivity in our our feet and our
hands and our toes and as a result again
leads to risk of infection endless risk
of injury to the feet and subsequently
amputation
and we know if we control blood sugar
levels and so our goal has been with
with management of both type 1 and type
2 diabetes is to lower those glucose
levels
and for the most part we we do that
through
a number well with type 2 diabetes
lifestyle modification and then
medications and i'll go into a little
bit more detail in a moment um after we
hear a little bit about from mark uh dr
swain about um why this is important
thanks marianne um so
when when you saw that that overview
that marianne showed the picture of of
the complications uh of type 2 diabetes
that really
that's a traditional picture and that
liver is not actually included on that
and so uh hopefully we're going to uh
um
uh
i i guess stress today that the liver
actually is
something that's that's intimately
involved in type 2 diabetes and what
what happens in in in the setting of a
number of things but type 2 diabetes one
of them is that you can develop fat in
the liver and if you look on the left
the liver becomes kind of yellow and a
bit swollen where normally it's kind of
pinky
and if you look at in a liver biopsy
it's sort of sort of microscopically the
normal liver is on the left you can see
nice little sort of liver cells which
are pink and they've got the nucleus
which is the blue bluey part in the
middle and they're all in little chains
like little little
blocks that are that are built in chains
and the blood flows between them and
that's where the exchange of nutrients
happen uh they're so important to
metabolism but if you look on the right
that's a liver that's that someone that
has or a biopsy from someone that has
fatty liver
and you can see the liver cells are
swollen and the white areas that look
like balloons they're actually cells
that have been expanded to be a balloon
shape uh by fat that's been deposited in
the cells and and and that fat can
actually lead to liver injury next slide
next slide please yeah thanks
um and so first of all so what is nafld
i mean not this is a a word that we use
today we use the word nash as well and
so it's important to define them so so
nafld is uh is a short form for what uh
the term non-alcoholic fatty liver
disease and so that means it's
essentially
a diagnosis a diagnosis of exclusion so
you remove the other cause of liver
disease including there's a certain
cutoff amount of alcohol consumption on
a daily basis that once you once you go
over that that level then then that
drives what we call alcohol related or
alcoholic fatty liver disease and uh and
how much alcohol that is is quite hotly
debated
however
you also can develop something called
nash
and nash is short form for
non-alcoholics theatro hepatitis
and and that is a very fancy term but
essentially steato just means fat and
hepatitis means inflammation so this
means
uh when when the fatty liver has become
a condition where the liver is inflamed
and being damaged
next slide
and and so when one's talking about
nafld or non-alcoholic fatty liver
disease it's important to recognize
they're actually talking about a
spectrum of liver diseases and that
ranges from fatty liver as i just showed
you that picture
to nash so nash is is is the fat
accumulating the liver that's associated
with inflammation or damage or
destruction of liver cells
and that destruction of liver cells can
lead to scarring in the liver and then
if you get enough scarring in the liver
that's what we call cirrhosis and if you
have enough cirrhosis then you can get
liver failure and also
and need a liver transplant or or it's a
it's a cause of liver related death but
also it predisposes people to developing
liver cancers and once you have
cirrhosis you have about a three percent
chance per year of developing a liver
cancer but uniquely in fatty liver
disease which is different than all the
other pretty much all the other liver
disease except for maybe hepatitis b
people can go just from having fatty
liver without cirrhosis even to
developing liver cancers and the
pictures at the top here just shows if
you look at the one on the right that
the pink is is is liver cells
and the blue is scar tissue and you can
see that the scar tissue or the blue is
surrounding the pink to make it look
nodular or like like lumps and that
lumpy bumpiness is what when people talk
about cirrhosis that's what they're
referring to is this sort of the size
the outside of the liver and inside all
through the liver becomes lumpy bumpy
and hard
next slide please
and so what are the main causes of of
non-alcoholic fatty liver disease well
as marianne said and this is often not i
think has been poorly recognized is that
diabetes is the main driver
and obesity those are the two
critical drivers of non-alcoholic fatty
liver disease although these other uh
things are cause there's some
medications that can lead to it there
are some genetic changes that can that
can drive fatty liver disease um people
that have high cholesterol or high
triglycerides which is another fat in
the blood they can also develop fatty
liver disease uh and
not usually an issue
in
western countries but rapid weight loss
can also
rarely cause uh uh fatty liver
next slide
uh and when you when you look at fatty
liver uh most people say oh i've never
heard of fatty liver disease i've never
heard of nafld or nash but in fact if
you look in north america so with a red
circle around you can see about 24 25 so
one in four people has fatty liver
disease
uh so it's extremely common it's growing
every year the the
the number of people in our society that
have fatty liver is growing
and when you look at nash so this
inflammation of the liver that's
associated with fat in the liver
that's also associated with the
development of scar tissue that affects
about two to three percent of the
general population
next slide
so what's the relationship between type
2 diabetes and math
next slide so so so mary ann showed that
the livers kind of plays an important
role in uh insulin sensitivity insulin
metabolism glucose metabolism um but but
there
there's growing evidence that that
there's a link between type 2 diabetes
and nafld and that is that that the
resistance to the effects of insulin the
body
which is really as marianne said
is the hallmark of type 2 diabetes so
the tissues don't respond to insulin
normally
that actually also leads to fat
accumulation in the liver so the
steatosis or non-alcoholic fatty liver
and when you look at people that have
type 2 diabetes
there's a
spectrum of studies that looked at this
but between 45 and probably closer to 75
percent of people with type 2 diabetes
have have have naffed or non-alcoholic
fatty liver disease
and this fat that accumulates in the
liver in the setting of type 2 diabetes
as i mentioned can lead to inflammation
or nash and liver damage and scarring
and when you look at people that have
type 2 diabetes they're more and and
they also have nafld they're more likely
to have nash so this liver inflammation
they're more likely to have liver
scarring and they're more likely to
progress to liver advanced liver
scarring so cirrhosis
and and and and also to develop liver
cancer
next slide
so what's so in the flipping it around
what's the link between nafl for having
fatty liver disease and type 2 diabetes
well people who have nafl so on an
ultrasound they're shown to have fatty
liver they're they're more insulin
resistant than those that don't have not
and when you look at people that have
naffle
they are two to threefold more likely to
develop type two diabetes over the next
five years
than those that don't have napple even
if they're not overweight
and people with a higher uh levels of
fatty livers or more steatosis
they're even more likely to develop type
2 diabetes and so the more fat one has
in the liver the more likely they are to
develop type 2 diabetes over time
and that risk is increased even further
if they also have associated liver scar
so
as i think marianne alluded to and i
think that picture that showed that that
that individual with the complications
of of uh diabetes traditionally
the approach to
finding and managing that when people
with type 2 diabetes has really been one
of i don't see anything here
and and the reason why i think is
because there was um
i think very limited understanding of it
i think there was a perception that it
was a benign thing that that would come
and go and didn't really uh drive any
sort of adverse liver uh outcomes
uh and and so it
was i i it was traditionally ignored
next slide
so so what's the real uh what's the
reality
uh is it that that we're making a big
thing out of nothing and and this is
actually just uh uh how we were managing
us in the past is the right way or is is
this
is this uh the zombie apocalypse and and
uh and this is something that's that
that that is that uh is a crisis
next slide
so
so when one looks at liver disease this
is this kind of shows what the liver on
the left is a normal liver that's f zero
means no scarring and as you go to the
right that's what is a liver specialist
what i'm most concerned about is you you
start to develop scarring in the liver
and when you get to f4 that's cirrhosis
when you get cirrhosis then you're much
more likely to develop liver cancer or
develop liver failure
and when you look at the drivers that
move people from the left to the right
type 2 diabetes is one of the key
drivers of that of that scarring in the
liver and that progression
and and that when you get that liver
fibrosis that's a key driver of poor
outcomes
so the question is if 45 to 75 of people
with type 2 diabetes have fatty liver or
nafl
how do we actually find those with
significant liver scarring so they can
they
that may benefit from seeing a liver
specialist recognizing what marianne
said was that most people are going to
have these other issues which are are
the things that are going to impact
their their lives more than fatty liver
disease well except the people that have
significant liver fibrosis
next slide
and so
one of the things we need to get better
at and and
and this is something where i think uh
uh people who manage individuals with
diabetes and people who who manage liver
disease especially
starting at a primary care family doctor
level is we need to develop and use
clinical care pathways
and case finding strategies so that we
can we can we can look at a at a large
group of people that have type 2
diabetes that are out in the community
seeing their family doctors and make
sure that the people with
nafld uh are are streamed in the most
appropriate care streams and usually
that will not involve the liver
specialist you know while someone's
helping to manage their their
cholesterol better their sugars better
and things like that because most of
them will not have significant liver
disease
excellent
and and i just want to highlight one
pathway that we developed in calgary and
through this pathway
that is really run by the family
physicians in calgary
is
we've been able to to you to funnel
individuals that are found to have fatty
livers some will have type 2 many but
happen of having type 2 diabetes and
another sort of 20 percent have are
pre-diabetic
we're able to funnel those
in to see a liver specialist if they're
found to have significant liver scarring
based on some very
sort of tests that can be done within
primary care and so it ends up that over
90 of the people that have fatty liver
never need to see a family a a liver
specialist as part of this pathway
next slide
so i'm going to
jump back a little bit to what do type 2
diabetes and what
how we we approach it and what our goals
are
so
with obesity
and um
and sedentary life being a huge
component a huge risk factor
for developing type 2 diabetes lifestyle
modification is number one in terms of
um treatment so we encourage people to
be active
to make sure that they're making good
dietary choices and i'll get into a
little bit more
um and hopefully with those lifestyle
modifications there'll be some weight
loss
and in people that we're not able to
achieve are to improve uh blood sugar
levels with either of those then we
consider medical therapy
there's oral medications there's
injectable medications and then there's
insulin therapy and i'll go into a
little bit more about each of these
next slide
so lifestyle modification
um and on the next slide i have a little
bit more detail um but it really is
about
um
making good dietary choices and people
patients will often ask me well what
what diet do you recommend what should i
be doing
we really encourage our patients to
follow the eating well um with canada's
food guide so a balanced diet and
everything in moderation
um
is there one diet that's better than
another really difficult to say
i often will tell my patients it's
whatever diet or whatever food plan
because diet also to me sometimes
implies that it's going to be a
short-term um
a short-term thing and that they can go
back eventually to their their their old
eating habits so whatever food plan they
can they can stick with and keep with i
think is going to be the most important
and the most successful
um in people who are overweight or or um
obese we do um recommend a nutritionally
balanced calorie reduced diet or food
plan um so that they do um lose weight
and then an intensive
behavior program maybe combining dietary
modification with increased activity and
what does increased activity mean so the
the um for diabetes canada recommends a
minimum of 150 minutes of moderate to
vigorous activity each week and and that
should be spread out over at least three
days so going out and doing a two-hour
walk one day of the week is really not
the the ideal um recommendation or
suggestion
ideally it's spread out over three days
and no more than two days without
exercise it's also important to really
reduce our i know it's hard in covert
times where everybody's working from
home and and i'm doing
a lot of online
meetings and things like that but it is
really important to avoid long periods
of time um
being sedentary so again to you know be
active for 30 minutes a day and then to
sit for the rest of the day is not the
ideal um situation so really important
to be as active um throughout the day as
possible and maybe breaking that up into
10 minutes three times a day which can
again be challenging but is probably
going to be more beneficial than just
clumping it to all at the starter at the
end of the day
um
resistance training is also um important
and it's recommended at least twice a
week preferably three times a week
in addition to the aerobic exercise
so really trying to be as active as
possible
next slide
and so in patients that aren't able to
control blood sugars with diet and
lifestyle and exercise we have we do we
do um uh treat them with uh
a very a
variety of different uh oral medications
um to start and and the order of how we
start this is really um gonna be
dependent on what else um what other
complications the patient has and we are
really
shifting towards a more patient-specific
regimen so i'm not going to really go
into too much about
when would we start this or when would
we start that but in terms of
medications that we have we have
medications like metformin that enhance
insulin sensitivity so they make the
liver more sensitive to the insulin
that's circulating so that the body
doesn't need to produce more insulin
that the insulin circulating
will be better recognized and function
better we have a medication like a
carbos that actually inhibits uptake of
glucose from the gut
um we have other medications like
secretogs that actually cause the body
to make more insulin um and then then
that insulin subsequently um works on
the liver to cause
and other tissues to cause the body to
um to use the glucose that's circulating
we have a newer class of oral
medications and injectables some of them
are injectable some of them are orals um
they're called incretin hormones and
these these medications work at the
level of the gut
and they
cause the body to actually
um create more of
jlp one hormone that is then circular
that then circulates and has other
effects outside of the gut and
specifically on the pancreas i'll get
into a bit more detail about that um to
help the pancreas um produce more more
insulin
um we also have a new group of
medications called sglt2 inhibitors
and again these these work differently
than all our other medications in that
they reduce the glucose reabsorption of
the level of kidney and cause the body
to excrete excess glucose
some older medications um called tzds
and these are
these are since uh also insulin
sensitizer not used very often these
days because there's been some concern
over cardiovascular
risks increased cardiovascular risks and
when all of these fail then often we'll
start to add insulin
and then again that just causes the body
to try and store
more of that circulating glucose
what's unique about these newer
medications so the sglt2 inhibitors as
well as the glp1 agonists is that they
actually lead to weight loss the sglt2
inhibitors will actually
prevent the reabsorption of glucose at
the level of the kidneys so you're
getting um
a loss of calories through
the kidney and urine this leads to
decreased fasting glucose levels
patients are more
less likely to have a rise in glucose
levels after a meal
their overall a1c which is our
long-term measurement of blood sugar
control is decreased suggesting better
blood sugar control they've also been
shown to have cardiovascular benefit and
not going to get into too much detail
there but important um in when we're
we're also talking about
um
nafld because we know with baffle
there's also increased cardiovascular
risk but these have increased
cardiovascular benefit and perhaps with
the weight loss that comes along with
this
is there a benefit on the liver
we don't know more more studies are
needed but there is the potential that
unlike some of their other older
medications that are causing the liver
to store more
um and perhaps maybe it
potentially could be exacerbating some
of the liver steatosis perhaps these
might actually have a benefit
glp-1 agonists as i started to mention
earlier
work differently than all our other
medications as well in that they work to
increase a hormone in the gut called
glp1
this hormone has a variety of different
effects
locally it causes a decrease in gastric
emptying so people feel full longer they
have increased satiety
it also works at the level of the brain
for to um
improve satiety as well so people feel
that they're more satisfied with less
food so tend to eat less
it works um
also at the level of the pancreas in
that it um increases insulin secretion
it decreases glucagon secretion so it's
causing the pancreas to work more
effectively more insulin circulating
helps to better control blood glucose
levels it helps with those beta cells so
those beta cells that are producing
insulin it causes an increased number of
beta cells it prevents beta cells from
dying off
it decreases
increases glucose uptake i think and
like the sglt2 inhibitors there's been
studies that have shown increased cardio
vascular protection
we know that weight loss comes along
with this
and potentially with all of these
benefits
uh improvements overall in uh liver
stantosis and i'm going to let mark talk
a little bit more about that but there's
been some preliminary studies that have
showed that
and it's definitely encouraging and
game-changing when we're thinking about
how we manage diabetes
one of the other benefits of both of
these medications is just that
often we're able to
use these medications and either get
patients off insulin or at least reduce
the amount of insulin that they're
taking and decreasing the amount of
insulin that they're taking is also
overall beneficial in terms of weight
loss and in terms of um the liver
and i'll hand it back over to mark now
thanks so thanks marianne so i'm going
to switch the management now just to
focus
as a liver specialist so i often focus
uh more on the on the liver which of
course you can see how these interact
and we need to have multi-disciplinary
approaches uh but the the the mainstay
of treatment is really quite similar to
treating type 2 diabetes is lifestyle
modification and targeting components of
the metabolic syndrome so obesity
hypertension hyperlipidemia next slide
uh and and when even though as a liver
specialist i have a tendency to focus on
on on the liver it's really important to
recognize that the liver
is not the biggest source of of
mortality or death in individuals with
type 2 diabetes it's
the complications that really mariam was
talking about so it's very important to
have optimal control of diabetes uh
control the high cholesterol and
triglycerides to treat high blood
pressure and then to do uh weight loss
strategies which include low
carbohydrate diets uh and the keto diets
the big one nowadays and uh low uh low
fructose so fructose is the main
sweetener in pot and pop is a huge
driver because humans don't metabolize
fructose and so it drives fat
into the liver which drives inflammation
next slide
i just want to uh there's a lot of
discussion these days about about the
mediterranean diet and i i think this is
quite relevant but here because as
marianne said i think the most important
thing is to find it's not a diet it's
it's it's a it's a it's a it's how you
like to eat that that suits you so you
can actually eat a healthy diet uh but
for when one's talking about uh weight
reduction in in the setting of nafld
you're really looking at about seven to
ten percent to start to really see the
beneficial effects on the liver and
around 10 percent to start to see
beneficial
beneficial effects with regards to
scarring
seventy percent seven percent to see
beneficial effects with regards to
inflammation and again there's a really
low carbohydrate low fat
or or different types of fat and so
vegetable not vegetables olive oil is
really a big driver of the mediterranean
diet and again reduced fructose
and the things that are listed here
under the mediterranean diet part fish
vegetables uh low sugar high fiber i
just also want to uh uh put it out there
that that there's a
growing epidemiological evidence that
coffee drinking is actually beneficial
from the for the liver point of view and
so if if i if patients come to me and
they're drinking coffee i actually
suggest they're even drinking more if
they if they can uh the important thing
is to recognize that if you're drinking
coffee and adding sugar like a double
double at tim hortons then that is
that's not actually drinking coffee
that's drinking sugar with cream and a
bit of coffee flavoring and so it's
really important to
to if you're going to drink coffee and
get the beneficial effect from it and
you should use non-sugar sweeteners and
try to use a low-fat
next slide
so what are the future farmer future
pharmacological therapies for for this
inflammation and scarring in the liver
associated with nap
well i just put this slide up to just
show you that there's a ton of therapies
out there in fact there's like
almost 800 clinical trials going on
across the world now for fatty liver
disease because this is such a huge
issue and they mainly target things uh
these different categories metabolic
anti-fibrotic anti-inflammatory i'm just
going to focus on two that i think are
relevant because they're the furthest
along and i think probably the most
exciting right now next slide
so what what are these liver directed
pharmacotherapies for patients with
nafld and nash the majority of whom are
going to have type 2 diabetes or insulin
insensitivity
next slide
so the first one is this drug called a
beta tocolic acid
and it's actually it's a bile acid
derivative and so our we have in our
bile is
in our bodies that we have bile acids
and they and they can stimulate a
receptor in our intestine called the fxr
receptor and this is a study that looked
at it over 72 weeks and what they found
with this so this is placebo in the blue
and then when you go to low dose and
sorry in the green the the low dose in
blue and the uh and the higher dose and
the pinkish color you can see in the top
bar that that there's an improvement in
in in scarring in the liver so fibrosis
is scarring and this is a one-stage
improvement so you can see that there's
actually this drug improves scarring in
the liver but interestingly if you look
at the bottom picture or bottom graph it
doesn't seem to change the inflammatory
component so they it shows us that
there's a differentiation between
impacting the inflammatory component
versus scarring and we don't understand
that very well at all
and it's relevant to the next slide
which is this this uh this drug that
marianne was talking about uh
semiglutids is a glp-1 agonist and
it's available to treat type 2 diabetes
and if you look on the on the left side
this is again treating with 72 weeks the
higher dose of semi glutathione 0.4
milligrams uh was significantly better
than the placebo in the in the gray bar
at
at making the inflammation in the liver
get better
however when you look in the right side
here it didn't seem to make any
difference with regards to liver
scarring
so again the they seem to be separate
and so the question about about these
type of drugs are do they impact if they
impact inflammation over enough time
maybe 72 weeks isn't enough time do they
actually also have a beneficial effect
on the scarring which is really what
we're most concerned about next slide
and that and i think that's that's
really the end of
what i have to say i think marianne as
well and uh
we're happy to take any questions and uh
answer any of your thoughts or comments
well thanks so much to both of you i'm i
can speak personally at least as someone
who lives with type 1 diabetes you know
i'm fascinated and it's it's not
something that i've been exposed to as a
complication or a comorbidity and it's
it's just really fascinating to learn
uh more about all these these
interconnections um so we do have quite
a number of questions we'll try to uh
tackle all of them um thanks everyone
for submitting your questions and being
curious uh while watching so the first
is
um
and and to answer folks just if you if
you feel that you have something you
would like to add just feel free to to
dive in we'll do a bit of a free-for-all
recognizing we just have the the two of
you so first question is uh how is nafld
diagnosed and how do you find out if you
have it or not so i think some probably
just looking for a bit of a
kick start or that first step of getting
a diagnosis
so traditionally uh
fatty liver actually was often not
diagnosed but nowadays i think if you if
you take people that have risk factors
for fatty liver and and the biggest risk
factors of course are are overweight
obesity and
type 2 diabetes or pre-diabetes and
but also people that have high
cholesterol or triglycerides those are
the people that are the highest risk
and
the probably the simplest way to
diagnose is if someone has an ultrasound
that shows fat in the liver that's fatty
liver
whether the liver tests are abnormal or
not
aryan do you have anything to add to
that
no not really i mean from a diet from an
endocrinologist perspective i will do i
will order um liver enzymes um on
patients if they're normal it doesn't
rule it out
but if it if they are elevated um i may
refer them on to um a hepatologist for
further investigation or for an
ultrasound
the interesting thing is in our in our
pathway in calgary we found that about
50 percent of people had persistently
normal liver tests that had fatty liver
that went back
over two years previous
and that the abnormal liver test did not
correlate with how much scarring they
ended up having in their
liver okay so we're we're learning a lot
about how to approach the uh
approach these patients i think there's
so much more that we need to understand
about how how to manage patients in a
way that really funnels them to the
right people because usually the right
person is not me
the next question is to do a little bit
with genetics which was alluded to you
know number of times as a potential risk
factor
the question is so here's a big one i
myself am type 1 my mom is type 2 and
has been diagnosed with fatty liver
disease that led to cirrhosis
does that then increase my risk
that's a very good question i don't have
a very good answer for that but but i
mean there are two different diseases
right that one's an autoimmune disease
and and although you can be a type 1
diabetic and also get insulin
you can also develop incidence and
insensitivity if you start to become
overweight and have those issues so you
can have this mixed pattern of kind of
like type two type one
uh and marianne would be the expert in
that uh but uh the uh um
i i don't think that
yeah
everything else considered that does not
would not place someone having type one
diabetes is of having the same
complications that
her mom had
yeah i would agree i mean i think that
you definitely can have uh
you can have type 1 diabetes with type 2
superimposed and we do see it we see
bariatric patients that have
type 1 diabetes and
requiring high high insulin
doses and post surgery aren't needing
the same type of insulin amounts post
bariatric surgery
so definitely it does does
occur
but are you at the same risk
if you don't have those other risk
factors i don't think so
have someone else who's wondering how
this topic relates to quote unquote
leaky liver
i have no clue because i don't even know
what leaky liver is but
when people get when people get
hyperglycemia so increased blood sugar
levels in the blood sugar levels
and they have nash so they don't but
they don't necessarily have to have
fatty liver uh it changes how the how
the cells that line the gut uh form a
barrier so normally our the cells that
line our gut are very good barrier for
bugs and products from bugs to getting
through that are really not good for us
and so what happens is that when you get
fatty liver or you get high like type 2
diabetes with high levels of of sugar
and you start to get an inflammation in
your body which goes along with that
it affects how how that barrier
functions so that it becomes leakier and
so and this felt to be that leakiness
can drive more inflammation in the body
which is which drives all of those uh
complicate many of those complications
that that marianne showed actually and
also drives worst liver disease
yeah we don't talk about
inflammation
often as part of one of the risk factors
but i think that there is
a significant amount of inflammation
that's happening that does lead to
increased insulin resistance whether
it's at the level of the gut um
definitely it was one of the of the
thoughts when i or
it is one of the thoughts with
infectious liver disease that the
chronic inflammation associated with
that increases insulin resistance and
leads to
increased risk of diabetes and there
have been cases where
you
treat their liver to treat their um
underlying infectious disease liver
disease so their hepatitis c and their
insulin needs actually improve because
there's decreased inflam with the
thought is decreased inflammation it's
not exactly well known but that's the
thought
um this next question is is probably
specific to mark and it's to do with the
the graphic you showed of the sort of
changing in color and
structure of the liver and it's someone
wondering can you can you fix the liver
and revert it to a nice pink one uh or
will it forever be damaged so that
that's a great question and uh
and so
the the liver is a fascinating organ in
that you can take a normal liver and
chop it in half and it grows back and so
it's the only organ that we have in our
body that regenerates so if the liver is
given an opportunity it regenerates and
so if if you can remove the damage then
the liver can get better but also people
used to think that scarring was
permanent but now we know there's
something called remodeling which means
that if the if you take away the ongoing
damage and the liver is able to pull
that scar tissue out as long as it's not
super well formed and super tight as if
it's a loose scar tissue and we know
from other liver diseases including
people that have profound weight loss
with bariatric surgery and things like
that that people can go from essentially
a serotic liver
to a liver that looks normal
is is it totally normal it's probably
not totally normal because there are
some other issues that go along with it
and the predisposition to cancers and
things like that if they already had
cirrhosis so really bad scarring that
probably gets less but probably doesn't
go back down to normal but the function
all those kind of things
uh and the sort of the more pinkiness as
the as the fat leaves the liver because
it's the pink that's the the yellow is
the fat not and that's what's changing
the color of the liver it would go back
to pink yes
that's that's fascinating i i didn't
know that the liver was regenerative
yeah it's pretty amazing and so that
that's actually the basis behind a liver
relating donor so when people get a
liver trap let's say you have advanced
uh
you're unfortunately have developed a
liver failure because of say napoleon
and someone in your family or whatever
can donate part of your liver and when
that liver is put in your body that
liver grows right to the same size that
your liver was before and the person
that donated the liver that their liver
goes right back to their same size their
liver was in their body
it's quite fascinating
well it's a miracle action
um we have someone wondering uh if blood
sugars are controlled through
medications despite still having sweets
is there a negative impact to the liver
in other words is it the level of sugar
consumed or the amount of sugar the body
needs to deal with that is most
detrimental to the liver
well that's a very i'll let marianne
take that action yeah that's a
complicated complicated question with a
complicated answer um definitely i think
when if you're having increased um
simple sugars sweets etc your blood
sugars are going up and depending on
what treatment you're on assuming let's
say you're on insulin you're taking
using more insulin and basically you're
actually causing the body to store
more
uh and the liver to store more so
you it could potentially be harmful and
we don't know that and i think that's
one of the things that um is
is different with some of these newer
medications is that they don't cause the
body to store more they cause you either
to to consume less
or to get rid of that excess um
uh glucose through the kidneys um and so
perhaps in those cases it wouldn't so i
really think it depends on the type of
medication you're on
and and potentially but potentially it
could cause more um aggravation in um
inflammation within the liver and more
fat to be accumulated
there's a question to do with um asking
if liver disease could be under
diagnosed uh if liver enzymes may not be
affected as it seems like the ultrasound
is done to only confirm the disease
yeah so liberty we know it's under
diagnosed right and and yeah an
interesting thing i have a discussion
all the time because i think that if you
go to most endocrinology practices they
say i don't see much liberties like i
don't see much end-stage liver disease
there's cirrhosis and i think that's
because endocrinologists are very good
broadly at controlling people's blood
sugar and they and they're focused at it
and they're very good at it and so their
and their goals of human government a1c
are relatively tight and sugar control
is tight but when you move away from a
specialist who's dedicated with that
move into into more sort of i guess into
a more of a community center setting
often the the the range of sugars that
are allowable that are that are okay are
are broader and the hemoglobin a1c
levels are often higher and i think as
in those individuals that where where
we're more likely to see uh because we
know that progressive liver disease is
related to
glucose control essentially uh in type 2
diabetics and so uh i think that's where
we're we see a lot of individual more
individuals that are going to be
presenting with with end stage liberties
and i can tell you as a liver specialist
we're seeing
many more people present now with liver
failure liver cancers that are that are
being driven by fatty liver disease not
by the traditional things like like
infectious hepatitis that we normally
would have thought as the key driver
so folks i think we have time for
probably one more question then we'll
have to have to wrap up but there's
there's one that frankly i'm curious
about this as well and i'll direct it to
mark and it's
why is coffee good for liver disease
what's the uh do you know more about
that
well it's interesting
so
caffeine broadly is beneficial to the
liver in that in that in that caffeine
stimulates a certain type of receptor
that's very important for blood flow to
the liver and that so that probably is a
beneficial effect of that
but it's more than just the caffeine
because it's actually if you look at if
you look at say caffeinated drinks that
that are not coffee they actually
um
have they seem to have a benefit but not
the same degree of benefit
as coffee and in fact there is even some
evidence that certain
ways of making coffee like a drip coffee
seems to be better than an instant
coffee and
so there's a lot left to be learned but
uh but but certainly i think it's if
someone likes coffee
i i don't think there's a downside
unless they have a heart issue or a
rhythm issue in their heart drinking
more coffee as long as they're not
adding sugar to it
okay that is it is really interesting
i've uh i'd like to before we wrap up
just sincerely thank you both uh it's
been such an interesting conversation i
you know i personally i've learned a lot
and i hope the same is true for uh for
our viewers and to our viewers i'd also
just like to say if you have further
questions please feel free to
visit diabetes.ca or to contact us
directly at 1 800 banting or info
diabetes.ta
um
you know i just once again really
sincere thank you to dr doyle and dr
swain and uh i'll also hand it over to
them to provide any any more information
on the canadian liver foundation
oh absolutely thank you for that it's uh
absolutely a great great conversation
very stimulating there and uh again for
more information i think both
organizations provide uh
quite a hefty amount of our resources
and support um for more information on
liver disease and all of disease we have
our liver.ca website that contains
all the information about fatty liver
disease and all the associated liver
diseases that dr swain
was indicating and speaking about
broadly
and we have also our email that
all patients and caregivers and those
who want more information to reach us
it's at clf liver.ca but again liver.ca
for additional information
okay thank you and once again thank you
everyone for your time and for sharing
that information greatly appreciated and
take care of everyone okay thank you so
much and thanks marianne that was really
a joy uh presenting with you
thank you too mark i enjoyed it as well
it was great
bye folks thank you thanks
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